Download Epidemiology and pathogenesis of Ebola viruses

48
REVIEW
Epidemiology and pathogenesis of Ebola viruses
Petr Michalek 1, Ludmila Krejcova 1, Vojtech Adam 1,2 and Rene Kizek 1,2 *
Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska
1, CZ-613 00 Brno, Czech Republic, European Union;
2
Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00
Brno, Czech Republic, European Union;
1
*Author to whom correspondence should be addressed; E-Mail: [email protected];
Received: 13.2.2015 / Accepted:9.3.2015 / Published: 1.4.2015
The family Filoviridae consists of three genera, the Ebolaviruses, Marburgviruses, and
the recently described Cuevaviruses. The two first of them belong among the most virulent
viruses. The Ebola viruses, respectively Zaire species of this genera is the causative agent
of the biggest ebola outbreak, namely West Africa Ebola Outbreak, which started in 2014,
and in which the case-mortality rate has been reported to be at about 50 percent, with the
number of total cases exceeding twenty-four thousands[1]. In comparison with earlier Ebola
outbreaks mortality have been higher (80 - 90 percent), but number of cases was a thousand
times lower. In this study will be presented epidemiology and pathogenesis of Ebola virus
disease including new findings resulting from the studies linked with 2014 Ebola Outbreak
in West Africa. The EVD epidemiology, pathogenesis, and clinical characterization will be
discussed in this study.
Keywords: Ebola virus, Ebola virus diseases , hemorrhagic fever, West Africa Ebola Outbreak
1. Basically about Ebola viruses
The Ebola viruses (EBOV) are enveloped, non-segmented, negative-sense, single-stranded
RNA viruses, with size of genome approximately 19 kbp [2]. The virion is pleomorphic, producing ‘U’- shaped, ‘6’-shaped, or circular forms
[3]. The EBOV may cause a disease in humans
as well as in non-human primates, called Ebola
virus disease (EVD). EBOV are firstly described
in 1976, since than five species of the EBOV
were described since. Four of them: Sudan virus
(SUDV), Ebola virus (EBOV, known as Zaire),
Taï Forest virus (TAFV), and Bundibugyo virus
(BDBV) cause acute and lethal disease in human population [4, 5]. The fifth, Reston virus
(RESTV), differs from each other, it has been
caused disease only in monkeys, chimpanzees,
and gorillas and it is apparently maintained
in an animal reservoir in the Philippines and
has not been found in Africa [6, 7]. Since 1976,
more than twenty outbreaks of EVD have been
reported in Africa [8]. The current outbreak,
West Africa Ebola Outbreak 2014 (WAEO),
first reported by the World Health Organization (WHO) on 22 March 2014, was caused by
ZEBOV and is responsible for more than ten
thousands death [9]. In addition to the three
most affected countries in sub-Saharan Africa
(Guinea, Liberia ad Sierra Leone), EBOV cases
have been reported in the Great Britain, the
United States and Spain [1, 10]. The behavior
of WAEO was so alarming, that some countries
decided to implement special measures for air
plane transport of passengers from affected
countries [11].
2. Ebola virus disease
EBOV cause severe hemorrhagic fever with
high percentage of fatal outcome in humans,
and several species of non-human primates
(NHPs) [12]. Human Ebola outbreaks usually
occur abruptly from a vaguely defined source,
with subsequent rapid spread from person to
person [13]. In the past, EBOV were classified
as „hemorrhagic fever viruses“, based on the
Michalek et al.
clinical manifestations, which include coagulation defects, bleeding, and shock [14, 15]. But
this term is no longer used because not all of
Ebola patients developed significant hemorrhage symptoms, which usually occurs only in
the terminal phase of fatal illness [16].
3. Epidemiology of EVD
Two main modes of transmission into human
populations have been suggested: either direct
contact to a reservoir or contact to other wildlife
that also contracts EBOV from the reservoir
[17]. Epidemiologic observations showed that
chimpanzees were the source of one human case
in two recently described outbreaks (Coˆte d’Ivoire in 1994 and Gabon in 1996) [13]. Transmission of EBOV in human population happens
by direct contact with infected blood, or other
bodily fluids (saliva, sweat, semen, milk), and
tissues from dead or living infected persons
[18]. Transmission via inanimate objects contaminated with infected bodily fluids is possible,
the principal mode of transmission in human
outbreaks is human-to-human transmission
through direct contact with a symptomatic or
dead EVD case or with contaminated surfaces
and materials (bedding, clothing) [19, 20]. The
risk for transmission is lower in the early stage
of human disease (prodromal phase), but viral
loads in blood and secretions rapidly increase
during the course of illness, with the highest
levels of virus shedding observed late in the
course of illness of severely ill patients [21,
22]. Burial ceremonies and handling of dead
bodies play an important role in transmission
[20]. Amplified transmission occurs in hospitals
(approximately one quarter of cases occurring
among health care workers) [6].
Human, non-human primates and some other
mammalian can be infected by EBOV and regarded as host, but reservoir of Ebola viruses was
for a long period hidden. An intensive efforts
were expend to identify the natural reservoir
[18]. Previously some researchers suggested,
rodents and bats could play role as reservoir
animals of EBOV [23, 24]. First report about
EBOV infected bats was verified by detection of
antibodies and viral RNA in three bats species
49
[25, 26]. What proved, that bats are involved in
circulation of EBOV in nature [27]. Transmission of EBOV to humans in sub-Saharan Africa
thought the contact with dead or living infected
animals (non-human primates, antelopes and
bats), although some studies traced cases back
to the skinning and butchering of carcasses
[28, 29]. Hunting and butchering of chimpanzee
and fruit bats has been identified in previous
outbreaks as a potential source of infection
[3, 7]. Leroy et al. presented, the human outbreaks consisted of multiple simultaneous epidemics caused by different viral strains, and
each epidemic resulted from the handling of a
distinct gorilla, chimpanzee, or duiker carcass
[30]. Due to this facts surveillance of wildlife health and monitoring of their mortality may help
to predict and prevent next Ebola outbreaks.
4. Clinical characterization and
pathogenesis of EVD
The incubation period of EVD ranges between
seven to ten days [31], but can be shorter (two
days) or longer (21 days) [7]. Virus presence in
blood is usually detectable one day before clinical symptoms appear, using polymerase-chain-reaction-based methods, increasing amounts
of virus in the bloodstream are accompanying
events of the fatal illness [32]. Case fatality
rates have varied from 44 to 90 percent, depending on the strain of EBOV, the level of medical
care, and public awareness, etc. [33]. Typically
clinical symptoms of EVD are sudden onset
of fever, accompanied by flu-like symptoms,
such as headache, malaise, myalgia, eventually
vomiting, and diarrhea [20]. Only in 30–50
percent of EVD patients developed hemorrhagic symptoms [34]. Severe cases of disease are
characterized by hepatic damage, renal failure
together with multi-organ dysfunction, and
central nervous system complication [7]. Mortality is caused by multi-organ failure and severe
bleeding sites [7, 35]. During the terminal phase
of illness, infected patients bleeding massively from the gastrointestinal tract affected by
disseminated intravascular coagulation are
relatively rare [7, 15]. Conversely, patients who
survive infection show a decrease in amounts
of circulating virus and clinical improvement
50
Journal of Metallomics and Nanotechnologies 2015, 1, 48—52
around day 7–10, what is usually linked with
the occurrence of EBOV-specific antibodies
[36]. Non-fatal or asymptomatic cases tend
to be associated with a specific IgM and IgG
responses and early and strong inflammatory
response, including interleukin β, interleukin 6,
and tumor necrosis factor α [7]. EBOV infected
animals showed renal lesions with disseminated
microvascular thrombosis evident in glomerular capillaries leading to acute kidney injury due
to hypoperfusion [37]. Minimal or mild changes
with no clinical significance were observed on
lungs as a respiratory failure is not a common feature of EBOV [38]. Lesions on livers of infected
macaques developed hepatic necrosis with mild
to moderate inflammation, moreover elevation
of hepatocellular and pancreatic enzymes are
frequently presented [39, 40].
The pathogenesis of the disease is still not
completely known. EBOV can enter the host
body mostly via mucosal surfaces, or injuries
in the skin [41]. Also infection through the
intact skin cannot be excluded, although it is
Figure 1: Overview of Ebola virus pathogenesis
considered unlikely. Aerosol infection (RESTV)
has been demonstrated in non-human primates
under experimental conditions in dispersion
chambers [42, 43]. EBOV infection is characterized by immune suppression and a systemic
inflammatory response, which could cause damage of the vascular, and immune systems, that
can lead to multiorgan failure and shock [7].
Geisbert et al. presented study in non-human
primates and showed that EBOV replicates in
monocytes, macrophages, and dendritic cells;
however, in situ hybridization and electron
microscopy have also shown the presence of
virus in endothelial cells, fibroblasts, hepatocytes, and adrenal cells [44]. Del Rio et al.
demonstrated, the EBOV disseminates to the
lymph nodes, liver, and spleen [6].
Michalek et al.
4. Conclusions
The understanding of EBOV pathogenesis
is crucial for the development of efficacious
treatments and vaccines. Targeted therapy
and vaccination are an immediate and highest
priority. The danger, hidden in high virulent and
infectious EBOV, breakdown of public health
and preventive measures, and create significant challenges ahead. Resolving all of issues
connected with EBOV will require long term
and collaboration of scientific community with
multinational organizations.
Acknowledgments
This work was supported by the FILODIAG
115844.
Conflicts of Interest
The authors declare they have no potential
conflicts of interests concerning drugs, products, services or another research outputs in
this study. The Editorial Board declares that the
manuscript met the ICMJE „uniform requirements“ for biomedical papers.
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